International Journal of Cardiology 187 (2015) 475–477
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
New-onset atrial fibrillation may be a more important predictor of cardiac mortality in acute myocardial infarction patients than preexisting atrial fibrillation☆,☆☆ Itsuro Morishima a, Toshiro Tomomatsu a, Kenji Okumura b,⁎, Takahito Sone a, Hideyuki Tsuboi a, Yasuhiro Morita a, Yosuke Inoue a, Ruka Yoshida a, Yoshimitsu Yura c, Toyoaki Murohara c a b c
Department of Cardiology, Ogaki Municipal Hospital, Ogaki, Japan Department of Cardiology, Tohno Kosei Hospital, Mizunami, Japan Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
a r t i c l e
i n f o
Article history: Received 23 March 2015 Accepted 24 March 2015 Available online 27 March 2015 Keywords: Acute myocardial infarction Atrial fibrillation Cardiac mortality Pump failure
Co-occurrence of atrial fibrillation (AF) with acute myocardial infarction (AMI) has been documented with increasing frequency, and its adverse impact on mortality is consistent with the observations reported by a recent review [1]. However, it is unclear whether Newonset and preexisting AF portend different risks. We recently encountered a patient with extensive AMI in whom hemodynamics were completely deteriorated by AF emergence despite mechanical supports and were fully recovered by sinus rhythm restoration by catheter ablation [2]. This case suggested the hypothesis that transition from the sinus rhythm to AF may be involved in the deterioration of heart failure leading to death in the short term following AMI onset. Accordingly, we estimated the impact of the two types of concomitant AF on the early trends in cardiac mortality The study population consisted of 732 consecutive AMI patients (age 69 ± 13 years old) seen at Ogaki Municipal Hospital. They were registered at admission, and all of them underwent emergent coronary angiography and they were, except 5, revascularized with percutaneous ☆ All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ The present study was not supported by any grant or by any external source of funding or industry sponsorship. ⁎ Corresponding author at: Tohno Kosei Hospital, 76-1 Tokicho, Mizunami 509-6101, Japan. E-mail address: [email protected] (K. Okumura).
http://dx.doi.org/10.1016/j.ijcard.2015.03.379 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
coronary intervention (n = 725) or with coronary bypass surgery (n = 2). Patients were monitored by telemetry during the index hospitalization. The study protocol complied with the Declaration of Helsinki and was approved by the local ethics committees of Ogaki Municipal Hospital. AF was defined as no discernible P waves and irregular RR intervals lasting at least 30 s. Patients were classified as having New-onset AF (n = 79. 10.8%) if they had no AF on admission, but had at least one episode of AF recorded on electrocardiography or telemetry. Patients observed with AF on hospital admission were classified as the Pre-AF group (n = 34, 4.6%). Patients with no evidence of AF during hospitalization belonged to the Non-AF group (n = 619, 84.6%). Overall mortality in the 90 days after AMI onset was 32%, 21%, and 8% in the New-onset AF, Pre-AF, and Non-AF groups, respectively. The prevalence of cardiac death in either of the New-onset AF and Pre-AF groups was significantly greater than that in the Non-AF group (P b 0.001 and P b 0.05, respectively, by an extension of Fisher's exact test). In particular, the prevalence of pump-failure death was much higher in the New-onset AF group (20% vs. 12% and 5% for Pre-AF and Non-AF, respectively). The log-rank test revealed that the survival only in the New-onset AF group was significantly reduced when compared with that in the NonAF group (Fig. 1). There was no statistical significance in mortality between the New-onset AF and Pre-AF groups. In a multivariate backward stepwise logistic regression model retaining parameters significant at the 0.05 level, higher Killip class, reduced eGFR and LVEF, anterior wall AMI, and New-onset AF were significantly associated with increasing cardiac death and pump-failure death (Table 1). Although AMI introduces left ventricular dysfunction, the presence of AF prior to the onset appears to be associated with previously exaggerated cardiovascular function compared with sinus rhythm and is often accompanied with the coexistence of chronic heart failure before AMI onset. AF may cause adverse hemodynamic effects, such as loss of atrial contraction, rapid ventricular rates, loss of atrioventricular synchrony, and an irregular RR interval, leading to a decrease in cardiac output [3,4]. So far, several studies have reported conflicting results regarding the prognostic differences between New-onset and preexisting AFs.
476
I. Morishima et al. / International Journal of Cardiology 187 (2015) 475–477
Fig. 1. Kaplan–Meier estimates for freedom from cardiac death (A) and pump-failure death (B) according to type of AF in patients with AMI. (A) *New-onset AF vs. Non-AF, P b 0.0001 by log-rank test. (B) *New-onset AF vs. Non-AF, P b 0.0001 by log-rank test.
Podolecki et al. demonstrated that permanent AF present before admission was an independent risk factor for death, but New-onset AF was not, when observation lasted 50 weeks after AMI onset [5]. Maagh et al. also indicated that patients with chronic AF had a higher mortality both during hospitalization and two years after discharge when compared with those with New-onset AF [6]. They followed the patients up to 25 months. In contrast to these studies, the GUSTO I trial based on 40,891 patients treated with thrombolytic therapy demonstrated that patients developing AF after admission had a significantly higher in-hospital and 30-day mortality rate than those who were admitted with AF before the PCI era [7]. Similarly, Behar et al. showed that the development of AF during hospitalization was associated with a higher mortality rate than chronic AF in the first 30 days [8]. A plausible interpretation of the controversial results can be given in the study conducted by Lau et al. in which they demonstrated that New-onset AF was associated with worse short-term outcomes while previous AF was more associated with mortality at long-term follow-up, when AF was divided by the previous presence of AF unlike our classification [9].
Table 1 Predictors of 90-day mortality by multivariate logistic regression analysis. Predictors Cardiac Death
Pump-failure death
Rhythm
Anterior MI Hyperlipidemia eGFR b 60 Killip class ≥ 3 LVEF Rhythm
Age Anterior MI Hyperlipidemia eGFR b 60 Killip class ≥ 3 LVEF
OR (95% CI) Non-AF New-onset AF Pre-AF
Non-AF New-onset AF Pre-AF
1 (reference) 2.81 (1.34–5.87) 1.35 (0.42–4.40) 1.98 (1.04–3.76) 0.38 (0.16–0.90) 2.74 (1.20–6.24) 4.02 (1.97–8.21) 0.95 (0.93–0.97) 1 (reference) 2.42 (1.10–5.37) 0.98 (0.25–3.91) 1.03 (0.99–1.07) 2.38 (1.14–4.94) 0.44 (0.16–1.21) 2.55 (1.11–7.77) 3.96 (1.89–8.29) 0.96 (0.94–0.99)
P-value 0.006 0.62 0.037 0.027 b0.001 0.001 b0.001 0.029 0.98 0.067 0.020 0.11 0.031 b0.001 b0.001
A backward stepwise logistic regression analysis was performed including all variables with P b 0.05 in the univariate analysis, but male sex and BMI were not significant after stepwise multivariate analysis. Hyperlipidemia was based on the presence of a low-density lipoprotein cholesterol level ≥140 mg/dl or a triglyceride level ≥150 mg/dl. AF, atrial fibrillation; BMI, body mass index; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; MI, myocardial infarction.
However, the underlying mechanisms, i.e., how New-onset AF is involved in cardiac mortality in the early phase of AMI, have not been fully elucidated by the above studies [10]. In this regard, the present study clearly demonstrated that New-onset AF is an independent predictor of pump-failure death, which comprised the majority of deaths due to cardiac causes. Among the survivors of the acute phase, the patients with preexisting AF, who generally have a higher comorbidity burden, may have a higher risk for cardiac death for the long-term period. In this study, both types of AF demonstrated significant impacts on cardiac death and pump-failure death. The prevalence of pump-failure death was much higher in the New-onset AF group than in the Pre-AF group. In multivariate logistic regression, New-onset AF was an independent predictor for cardiac death or pump-failure death while preexisting AF was not; worse Killip class, renal function, and LVEF were also independent predictors of these death categories. The clinical implications of these findings are that patients with New-onset AF should receive more attention in terms of secondary prevention of adverse cardiac events, especially, worsening of congestive heart failure that could be fatal, than those with preexisting AF in the early phase of AMI. In conclusion, New-onset AF, rather than preexisting AF, is an independent predictor for cardiac death mainly through worsening pump failure during short-term follow-up of 90 days after AMI onset. In the setting of AMI, the emergence of AF should be regarded as a sign of subsequent critical cardiac events. Conflict of interest None declared. References [1] P. Jabre, V.L. Roger, M.H. Murad, et al., Mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis, Circulation 123 (2011) 1587–1593. [2] I. Morishima, T. Sone, H. Tsuboi, H. Mukawa, Rescue pulmonary vein isolation for hemodynamically unstable atrial fibrillation storm in a patient with an acute extensive myocardial infarction, BMC Cardiovasc. Disord. 12 (2012) 110. [3] D.M. Clark, V.J. Plumb, A.E. Epstein, G.N. Kay, Hemodynamic effects of an irregular sequence of ventricular cycle lengths during atrial fibrillation, J. Am. Coll. Cardiol. 30 (1997) 1039–1045. [4] K. Stamboul, M. Zeller, L. Fauchier, et al., Incidence and prognostic significance of silent atrial fibrillation in acute myocardial infarction, Int. J. Cardiol. 174 (2014) 611–617. [5] T. Podolecki, R. Lenarczyk, J. Kowalczyk, et al., Effect of type of atrial fibrillation on prognosis in acute myocardial infarction treated invasively, Am. J. Cardiol. 109 (2012) 1689–1693.
I. Morishima et al. / International Journal of Cardiology 187 (2015) 475–477 [6] P. Maagh, T. Butz, I. Wickenbrock, et al., New-onset versus chronic atrialfibrillation in acute myocardial infarction: differences in short- and long-term follow-up, Clin. Res. Cardiol. 100 (2011) 167–175. [7] B.S. Crenshaw, S.R. Ward, C.B. Granger, A.L. Stebbins, E.J. Topol, R.M. Califf, Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I experience, J. Am. Coll. Cardiol. 30 (1997) 406–413. [8] S. Behar, Z. Zahavi, U. Goldbourt, H. Reicher-Reiss, Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction. SPRINT Study Group, Eur. Heart J. 13 (1992) 45–50.
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[9] D.H. Lau, L.T. Huynh, D.P. Chew, et al., Prognostic impact of types of atrial fibrillation in acute coronary syndromes, Am. J. Cardiol. 104 (2009) 1317–1323. [10] F. Angeli, G. Reboldi, M. Garofoli, et al., Atrial fibrillation and mortality in patients with acute myocardial infarction: a systematic overview and meta-analysis, Curr. Cardiol. Rep. 14 (2012) 601–610.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
New-onset atrial fibrillation may be a more important predictor of cardiac mortality in acute myocardial infarction patients than preexisting atrial fibrillation☆,☆☆ Itsuro Morishima a, Toshiro Tomomatsu a, Kenji Okumura b,⁎, Takahito Sone a, Hideyuki Tsuboi a, Yasuhiro Morita a, Yosuke Inoue a, Ruka Yoshida a, Yoshimitsu Yura c, Toyoaki Murohara c a b c
Department of Cardiology, Ogaki Municipal Hospital, Ogaki, Japan Department of Cardiology, Tohno Kosei Hospital, Mizunami, Japan Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
a r t i c l e
i n f o
Article history: Received 23 March 2015 Accepted 24 March 2015 Available online 27 March 2015 Keywords: Acute myocardial infarction Atrial fibrillation Cardiac mortality Pump failure
Co-occurrence of atrial fibrillation (AF) with acute myocardial infarction (AMI) has been documented with increasing frequency, and its adverse impact on mortality is consistent with the observations reported by a recent review [1]. However, it is unclear whether Newonset and preexisting AF portend different risks. We recently encountered a patient with extensive AMI in whom hemodynamics were completely deteriorated by AF emergence despite mechanical supports and were fully recovered by sinus rhythm restoration by catheter ablation [2]. This case suggested the hypothesis that transition from the sinus rhythm to AF may be involved in the deterioration of heart failure leading to death in the short term following AMI onset. Accordingly, we estimated the impact of the two types of concomitant AF on the early trends in cardiac mortality The study population consisted of 732 consecutive AMI patients (age 69 ± 13 years old) seen at Ogaki Municipal Hospital. They were registered at admission, and all of them underwent emergent coronary angiography and they were, except 5, revascularized with percutaneous ☆ All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ The present study was not supported by any grant or by any external source of funding or industry sponsorship. ⁎ Corresponding author at: Tohno Kosei Hospital, 76-1 Tokicho, Mizunami 509-6101, Japan. E-mail address: [email protected] (K. Okumura).
http://dx.doi.org/10.1016/j.ijcard.2015.03.379 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
coronary intervention (n = 725) or with coronary bypass surgery (n = 2). Patients were monitored by telemetry during the index hospitalization. The study protocol complied with the Declaration of Helsinki and was approved by the local ethics committees of Ogaki Municipal Hospital. AF was defined as no discernible P waves and irregular RR intervals lasting at least 30 s. Patients were classified as having New-onset AF (n = 79. 10.8%) if they had no AF on admission, but had at least one episode of AF recorded on electrocardiography or telemetry. Patients observed with AF on hospital admission were classified as the Pre-AF group (n = 34, 4.6%). Patients with no evidence of AF during hospitalization belonged to the Non-AF group (n = 619, 84.6%). Overall mortality in the 90 days after AMI onset was 32%, 21%, and 8% in the New-onset AF, Pre-AF, and Non-AF groups, respectively. The prevalence of cardiac death in either of the New-onset AF and Pre-AF groups was significantly greater than that in the Non-AF group (P b 0.001 and P b 0.05, respectively, by an extension of Fisher's exact test). In particular, the prevalence of pump-failure death was much higher in the New-onset AF group (20% vs. 12% and 5% for Pre-AF and Non-AF, respectively). The log-rank test revealed that the survival only in the New-onset AF group was significantly reduced when compared with that in the NonAF group (Fig. 1). There was no statistical significance in mortality between the New-onset AF and Pre-AF groups. In a multivariate backward stepwise logistic regression model retaining parameters significant at the 0.05 level, higher Killip class, reduced eGFR and LVEF, anterior wall AMI, and New-onset AF were significantly associated with increasing cardiac death and pump-failure death (Table 1). Although AMI introduces left ventricular dysfunction, the presence of AF prior to the onset appears to be associated with previously exaggerated cardiovascular function compared with sinus rhythm and is often accompanied with the coexistence of chronic heart failure before AMI onset. AF may cause adverse hemodynamic effects, such as loss of atrial contraction, rapid ventricular rates, loss of atrioventricular synchrony, and an irregular RR interval, leading to a decrease in cardiac output [3,4]. So far, several studies have reported conflicting results regarding the prognostic differences between New-onset and preexisting AFs.
476
I. Morishima et al. / International Journal of Cardiology 187 (2015) 475–477
Fig. 1. Kaplan–Meier estimates for freedom from cardiac death (A) and pump-failure death (B) according to type of AF in patients with AMI. (A) *New-onset AF vs. Non-AF, P b 0.0001 by log-rank test. (B) *New-onset AF vs. Non-AF, P b 0.0001 by log-rank test.
Podolecki et al. demonstrated that permanent AF present before admission was an independent risk factor for death, but New-onset AF was not, when observation lasted 50 weeks after AMI onset [5]. Maagh et al. also indicated that patients with chronic AF had a higher mortality both during hospitalization and two years after discharge when compared with those with New-onset AF [6]. They followed the patients up to 25 months. In contrast to these studies, the GUSTO I trial based on 40,891 patients treated with thrombolytic therapy demonstrated that patients developing AF after admission had a significantly higher in-hospital and 30-day mortality rate than those who were admitted with AF before the PCI era [7]. Similarly, Behar et al. showed that the development of AF during hospitalization was associated with a higher mortality rate than chronic AF in the first 30 days [8]. A plausible interpretation of the controversial results can be given in the study conducted by Lau et al. in which they demonstrated that New-onset AF was associated with worse short-term outcomes while previous AF was more associated with mortality at long-term follow-up, when AF was divided by the previous presence of AF unlike our classification [9].
Table 1 Predictors of 90-day mortality by multivariate logistic regression analysis. Predictors Cardiac Death
Pump-failure death
Rhythm
Anterior MI Hyperlipidemia eGFR b 60 Killip class ≥ 3 LVEF Rhythm
Age Anterior MI Hyperlipidemia eGFR b 60 Killip class ≥ 3 LVEF
OR (95% CI) Non-AF New-onset AF Pre-AF
Non-AF New-onset AF Pre-AF
1 (reference) 2.81 (1.34–5.87) 1.35 (0.42–4.40) 1.98 (1.04–3.76) 0.38 (0.16–0.90) 2.74 (1.20–6.24) 4.02 (1.97–8.21) 0.95 (0.93–0.97) 1 (reference) 2.42 (1.10–5.37) 0.98 (0.25–3.91) 1.03 (0.99–1.07) 2.38 (1.14–4.94) 0.44 (0.16–1.21) 2.55 (1.11–7.77) 3.96 (1.89–8.29) 0.96 (0.94–0.99)
P-value 0.006 0.62 0.037 0.027 b0.001 0.001 b0.001 0.029 0.98 0.067 0.020 0.11 0.031 b0.001 b0.001
A backward stepwise logistic regression analysis was performed including all variables with P b 0.05 in the univariate analysis, but male sex and BMI were not significant after stepwise multivariate analysis. Hyperlipidemia was based on the presence of a low-density lipoprotein cholesterol level ≥140 mg/dl or a triglyceride level ≥150 mg/dl. AF, atrial fibrillation; BMI, body mass index; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; MI, myocardial infarction.
However, the underlying mechanisms, i.e., how New-onset AF is involved in cardiac mortality in the early phase of AMI, have not been fully elucidated by the above studies [10]. In this regard, the present study clearly demonstrated that New-onset AF is an independent predictor of pump-failure death, which comprised the majority of deaths due to cardiac causes. Among the survivors of the acute phase, the patients with preexisting AF, who generally have a higher comorbidity burden, may have a higher risk for cardiac death for the long-term period. In this study, both types of AF demonstrated significant impacts on cardiac death and pump-failure death. The prevalence of pump-failure death was much higher in the New-onset AF group than in the Pre-AF group. In multivariate logistic regression, New-onset AF was an independent predictor for cardiac death or pump-failure death while preexisting AF was not; worse Killip class, renal function, and LVEF were also independent predictors of these death categories. The clinical implications of these findings are that patients with New-onset AF should receive more attention in terms of secondary prevention of adverse cardiac events, especially, worsening of congestive heart failure that could be fatal, than those with preexisting AF in the early phase of AMI. In conclusion, New-onset AF, rather than preexisting AF, is an independent predictor for cardiac death mainly through worsening pump failure during short-term follow-up of 90 days after AMI onset. In the setting of AMI, the emergence of AF should be regarded as a sign of subsequent critical cardiac events. Conflict of interest None declared. References [1] P. Jabre, V.L. Roger, M.H. Murad, et al., Mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis, Circulation 123 (2011) 1587–1593. [2] I. Morishima, T. Sone, H. Tsuboi, H. Mukawa, Rescue pulmonary vein isolation for hemodynamically unstable atrial fibrillation storm in a patient with an acute extensive myocardial infarction, BMC Cardiovasc. Disord. 12 (2012) 110. [3] D.M. Clark, V.J. Plumb, A.E. Epstein, G.N. Kay, Hemodynamic effects of an irregular sequence of ventricular cycle lengths during atrial fibrillation, J. Am. Coll. Cardiol. 30 (1997) 1039–1045. [4] K. Stamboul, M. Zeller, L. Fauchier, et al., Incidence and prognostic significance of silent atrial fibrillation in acute myocardial infarction, Int. J. Cardiol. 174 (2014) 611–617. [5] T. Podolecki, R. Lenarczyk, J. Kowalczyk, et al., Effect of type of atrial fibrillation on prognosis in acute myocardial infarction treated invasively, Am. J. Cardiol. 109 (2012) 1689–1693.
I. Morishima et al. / International Journal of Cardiology 187 (2015) 475–477 [6] P. Maagh, T. Butz, I. Wickenbrock, et al., New-onset versus chronic atrialfibrillation in acute myocardial infarction: differences in short- and long-term follow-up, Clin. Res. Cardiol. 100 (2011) 167–175. [7] B.S. Crenshaw, S.R. Ward, C.B. Granger, A.L. Stebbins, E.J. Topol, R.M. Califf, Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I experience, J. Am. Coll. Cardiol. 30 (1997) 406–413. [8] S. Behar, Z. Zahavi, U. Goldbourt, H. Reicher-Reiss, Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction. SPRINT Study Group, Eur. Heart J. 13 (1992) 45–50.
477
[9] D.H. Lau, L.T. Huynh, D.P. Chew, et al., Prognostic impact of types of atrial fibrillation in acute coronary syndromes, Am. J. Cardiol. 104 (2009) 1317–1323. [10] F. Angeli, G. Reboldi, M. Garofoli, et al., Atrial fibrillation and mortality in patients with acute myocardial infarction: a systematic overview and meta-analysis, Curr. Cardiol. Rep. 14 (2012) 601–610.
